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Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats

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Abstract

Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are desperately needed. In the present study, the anti-diabetic and renoprotective effects of aliskiren have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats were divided into four groups; normal, diabetic, diabetic treated with gliclazide (10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day) for 1 month. At the end of the experiment, mean arterial blood pressure and heart rate were recorded. Rats were then euthanized and serum was separated for determination of glucose, insulin, kidney function tests, superoxide dismutase activity (SOD), adiponectin, and tumor necrosis factor-alpha (TNF-α). One kidney was used for estimation of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) contents. Other kidney was used for histopathological study and immunohistochemical measurement of caspase-3 and transforming growth factor beta (TGF-β). In addition, islets of Langerhans were isolated from normal rats by collagenase digestion technique for in vitro study. Aliskiren normalized STZ-induced hyperglycemia, increased insulin level both in vivo and in vitro, normalized kidney function tests and blood pressure, and alleviated STZ-induced kidney histopathological changes. This could be related to the ability of aliskiren toward preserving hemodynamic changes and alleviating oxidative stress and inflammatory and apoptotic markers induced by STZ in rats. However, aliskiren was more effective than gliclazide in relieving STZ-induced DN. These findings support the beneficial effect of aliskiren treatment in DN which could be attributed to its anti-diabetic, renoprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects. Moreover, clinical studies are required to establish the effectiveness of aliskiren treatment in patients suffering from hypertension and diabetes.

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Abbreviations

ACEIs:

Angiotensin converted enzyme inhibitors

ARB:

Angiotensin II receptor blocker

BUN:

Blood urea nitrogen

DM:

Diabetes mellitus

DN:

Diabetic nephropathy

GSH:

Reduced glutathione

HR:

Heart rate

MDA:

Malondialdehyde

MAP:

Mean arterial pressure

NO:

Nitric oxide

PRA:

Plasma renin activity

RAAS:

Renin-angiotensin aldosterone system

ROS:

Reactive oxygen species

STZ:

Streptozotocin

SOD:

Superoxide dismutase activity

TGF-β:

Transforming growth factor-beta

TNF-α:

Tumor necrosis factor-alpha

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Contribution statement

HA and AM conceived and designed the study and conducted the systematic review. AM conducted the statistical analysis and drafted the paper. AM and LA contributed to interpreting the findings and revised the paper. NH, AS, and HA are involved in the critical revision of the paper. All authors edited and approved the final version of the manuscript to be published. AM had full access to data in the study and had final responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. Department of Pharmacology, National Organization for Drug Control and Research (NODCAR), Giza, 35521, Egypt

    Amal M. Mahfoz & Nahed M. Hassanein

  2. Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo, 11562, Egypt

    Amal M. Mahfoz

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt

    Hekma A. Abd El-Latif, Lamiaa A. Ahmed & Afaf A. Shoka

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  1. Amal M. Mahfoz
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  2. Hekma A. Abd El-Latif
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  3. Lamiaa A. Ahmed
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  4. Nahed M. Hassanein
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  5. Afaf A. Shoka
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Correspondence to Amal M. Mahfoz.

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Mahfoz, A.M., El-Latif, H.A.A., Ahmed, L.A. et al. Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats. Naunyn-Schmiedeberg's Arch Pharmacol 389, 1315–1324 (2016). https://doi.org/10.1007/s00210-016-1299-2

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